DESCRIPTION: (Applicant's Abstract) This grant was written in response to NIDA program announcement PA 94-007 which stresses the importance of secondary analysis research focusing of the development of methodology for investigating the etiology of drug use/abuse. Although PA 94-007 recommends secondary analyses of national epidemiological databases, research that directly targets the family as the unit of analysis may be critical for investigating the etiology of substance abuse and related behaviors. The Adolescent Substance Abuse (ASA) family study (DA-05131-04) is uniquely suited for investigating these issues. Families are recruited through identified male adolescent probands who are consecutive admissions to a residential treatment facility for substance abuse and delinquency. In addition, control probands and their families are matched by age, ethnicity and zipcode of residence to the treatment probands. This unique design allows for modeling ascertainment selection in the treatment families, and provides important comparisons between the highly selected and unselected adolescents and their families. The database is extensive, providing information from direct interviews, self-report questionnaires, and family history reports regarding use/abuse of multiple substances and comorbid psychopathology. The Principal Investigator has worked extensively with the ASA family study data for the past 18 months (Individual National Research Service Award: DA-05570-01), and has played an integral role in managing the database and in developing statistical methods for the analysis of complex family pedigree data. The primary purposes of this proposal are: 1) to request funding for secondary analyses of the ASA database to continue the development of state-of-the-art statistical methodologies for investigating the etiology of individual differences in substance abuse and comorbid psychopathology; and 2) to obtain pilot data on female adolescent substance abusers to investigate gender differences in the expression of familial liability and comorbidity in preparation for adding a female proband component to the ASA study.